Peptide Treatment for Pemphigus Foliaceus

Pemphigus vulgaris (PV) is a rare but potentially life-threatening disease characterized by the development of large, painful blisters on the skin and other soft membranes such as those of the mouth. The skin itself is weakened and easily peeled away from the body, exposing the patient to infection. Currently available treatments are aimed at controlling symptoms rather than curing the disease, but since the mid-2000s peptide-based treatments have been under development that address the underlying autoimmune response that causes PV.

Underlying Cause of Disease

• The peptide-based treatments being developed are based on an improved understanding of the underlying disease. It is now known that PV is an autoimmune disease in which the body produces antibodies that attack its own “desmoglein-3,” a protein that helps to hold skin cells together. The antibodies specifically target the portion of the protein where it interacts with the same protein on neighboring cells, causing the skin to break apart and triggering local inflammation, according to the Journal of Immunology 2008 and the Journal of Translational Medicine 2006.

Peptide Immunotherapy

• One new approach to treating PV is with peptide immunotherapy. In peptide immunotherapy, the patient is administered a peptide, or short protein sequence, with an amino acid sequence identical to a portion of the desmoglein-3 protein with which the PV antibodies interact. The rationale behind the treatment is that exposing the immune system to increased levels of the protein sequence will evoke immune system tolerance of it. Because of its similarity to the rationale behind vaccination, this type of treatment is sometimes called a “peptide vaccine.”

PI-0824

• A company called Peptimmune has developed one such peptide, designated PI-0824. In 2005, the company completed phase I clinical testing of PI-0824, which established its safety but produced no evidence of reduced autoimmune response. In this study, 15 patients each received two intravenous doses of the drug. New studies exploring the efficacy of the therapy at higher dosages have been planned according to the company's website, but no information has been published as of July 2010.

DSG3-49-60

• In 2006, Giovanni Angelini and other researchers published a study in the “Journal of Translational Medicine” describing the initial clinical test of a new peptide immunotherapy for PV, DSG3-49-60. The researchers tested a topical formulation of their peptide on a single patient with difficult-to-treat PV. At the end of the one-week treatment period, the peptide-treated blister showed reduced redness and greater evidence of healing relative to the conventionally treated blister. Interestingly, the patient improved clinically overall and the improvement persisted long after the treatment; however, because only one patient was tested, it is impossible to know if the peptide treatment played a role in the improvement.

Future Testing

• As of July 2010, no further clinical studies have appeared in the medical literature since the 2006 study. However, as indicated by reviews in “Drugs and Aging” (2009) and “American Journal of Clinical Dermatology” (2008), the potential of peptide immunotherapy for PV is clearly of interest to the PV research community. Both reviews indicate that further testing is necessary to determine the efficacy of this type of treatment for PV, as well as its benefits relative to other emerging treatments.

Summary

• If efficacy is established, peptide immunotherapy still faces the obstacle of high manufacturing costs. Also, as discussed by Kurzan and Brenner in the journal “Autoimmunity” (2006), there is still debate in the scientific community whether antibodies against other proteins may also be involved in the disease. An anti-desmoglein-3 peptide may not affect that portion of the autoimmune response. However, the fact that significant adverse effects were not observed in either study is in itself encouraging, since the use of antigenic peptides has sometimes been shown in past studies to evoke a strong allergic response, according to the Journal of Translational Medicine 2004. The exploration of peptide immunotherapy appears to be one step toward improved treatment of PV.